Activation of factor VIII by factor IXa.
Thrombin causes an increase in factor VIII coagulant (VIII:C) activity, which is followed by a decay of VIII:C activity to below baseline levels. It has been suggested that a similar interaction of trace amounts of thrombin and factor VIII is a necessary prerequisite before factor VIII can participate in the coagulation cascade. In the current study, factor IXa, a serine protease with structural similarities to thrombin, is shown to cause an increase and subsequent fall in VIII:C in a manner qualitatively similar to the reaction with thrombin. The reaction is inhibited by a human inhibitor to factor IX and the interaction appears to involve only VIII:C, since factor-VIII-related protein (VIII:RP) is not changed on polyacrylamide gel electrophoresis (PAGE) or radioimmunoassay during the reaction. Phospholipid increases the activation of factor VIII by factor IXa, and high concentrations of diisopropylfluorophosphate and hirudin inhibit the reaction. The physiologic significance of the interaction of factor IXa with factor VIII is not entirely clear since the concentration of factor IXa needed for activation is much greater than the concentration of thrombin required for similar activation of factor VIII. Factor IXa is most likely to play a role in the intrinsic cascade acting as an initial activator of factor VIII, since factor IXa precedes thrombin in this clotting sequence. In addition, factor IXa may be important wherever relatively high local concentrations of factor IXa and factor VIII occur, particularly in the presence of phospholipid, which may serve to localize the coagulation factors.
D000818:Animals; D001780:Blood Coagulation Tests; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D005164:Factor IX / Q000276:immunology / Q000502:physiology*; D015949:Factor IXa; D005169:Factor VIII / Q000032:analysis* / Q000037:antagonists & inhibitors; D015944:Factor VIIIa; D006801:Humans; D010743:Phospholipids / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013696:Temperature; D013917:Thrombin / Q000494:pharmacology
D010743:Phospholipids; D011480:Protease Inhibitors; D015944:Factor VIIIa; D005169:Factor VIII; D005164:Factor IX; D015949:Factor IXa; D013917:Thrombin; D002118:Calcium